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Pregnancy
Published in T. Yee Khong, Annie N. Y. Cheung, Wenxin Zheng, Richard Wing-Cheuk Wong, Hao Chen, Diagnostic Endometrial Pathology, 2019
T. Yee Khong, Annie N. Y. Cheung, Wenxin Zheng
There are two subsets of extravillous trophoblast: one subset, termed the interstitial trophoblast, infiltrates the interstitium of the decidua while the other, termed the endovascular trophoblast, infiltrates the spiral arteries (Figure 3.3). This population of interstitial and endovascular trophoblast, sometimes also called intermediate trophoblast, is a mixture of mononuclear cytotrophoblast, multinuclear syncytiotrophoblast and cells that are truly intermediate in form.
Gestational trophoblastic neoplasia
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2014
Fieke E.M. Froeling, Michael J. Seckl
Epithelioid trophoblastic tumour is a recently described neoplastic proliferation of intermediate trophoblast that is thought by some investigators to be distinct from PSTT and choriocarcinoma. It has been proposed that ETT arises from the intermediate trophoblasts of the chorionic leaves.41 Histologically, ETT displays a relatively uniform, nodular proliferation of intermediate-sized epithelioid trophoblasts, forming nests and cords. Islands of trophoblast are typically surrounded by areas of hyalinization or eosinophilic debris simulating tumour cell necrosis, resembling keratinous material in a squamous cell carcinoma. ETT can furthermore be associated with focal replacement of the cervical glandular epithelium with stratified neoplastic cells, simulating squamous cervical intra-epithelial neoplasia. The cells are positive for cytokeratin, epithelial membrane antigen and inhibin-a, whereas trophoblastic markers hPL, hCG and melanoma cell adhesion molecule are only focally expressed.48 Whether ETT is really a clinically distinct disease entity from PSTT in the GTD spectrum remains unclear.49
Gestational Trophoblastic Neoplasia
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
PSTT accounts for 0.2% of all GTD43,44 and is thought to derive from the intermediate trophoblasts at the implantation site.45 PSTT, like choriocarcinoma, can arise after any type of pregnancy, including term delivery, ectopic, miscarriage, CHM, or PHM.46 The causative pregnancy may not be the immediate antecedent pregnancy. Genetic analysis of some PSTTs has demonstrated that they are mostly diploid, either originating from a normal conceptus, and therefore biparental, or androgenetic, from a CHM.34,43,47–50 A tetraploid PSTT has been described.49 Interestingly, for reasons that are unclear, most PSTTs and ETTs that arise after a non-molar pregnancy are female in origin.51 PSTTs display a pattern of vascular invasion, characterized by neoplastic cells migrating through, and replacing, vessel walls while maintaining the overall vascular architecture. PSTTs are slow-growing malignant tumors of intermediate trophoblast and so produce little hCG. However, they often stain strongly for human placental lactogen (hPL) and β1-glycoprotein. Elevated Ki-67 levels may help in distinguishing PSTT from a regressing placental nodule or exaggerated placental-site reaction.52 Whereas a low level of Ki-67 labelling (<1%) is seen in an exaggerated placental site, PSTTs generally show a higher index (>10%). In contrast to other forms of GTN, spread tends to occur late by local infiltration, hematogenously, and unlike other forms of GTN, also sometimes via the lymphatics.53
Current chemotherapeutic options for the treatment of gestational trophoblastic disease
Published in Expert Opinion on Pharmacotherapy, 2023
Antonio Braga, Gabriela Paiva, Cassia Juliana Cattai, Kevin M. Elias, Neil S. Horowitz, Ross S. Berkowitz
GTN includes the following histopathological forms: invasive mole (IM), choriocarcinoma (CCA), placental site trophoblastic tumor (PSTT), and epithelioid trophoblastic tumor (ETT), encompassing lesions that originate in the chorionic villi and the extravillous trophoblast, which differ in regard to treatment and prognosis [3,4]. The presence of chorionic villi in the myometrium, with or without vascular invasion, characterizes the invasive mole, and choriocarcinoma is commonly responsible for metastatic disease, which occurs in 30% of GTN cases. Hematogenous dissemination is responsible for pulmonary and genital involvement, although any other organ can be affected, notably the liver and brain [3,4]. PSTT and ETT are the rarest forms of GTN and originate from nonvillous trophoblastic lesions, derived from the intermediate trophoblast. These forms present biochemical and therapeutic differences when compared to invasive mole and choriocarcinoma, as they exhibit low hCG levels and limited response to chemotherapy, making surgery mandatory in these cases [5,6].
Human papillomavirus in foetal and maternal tissues from miscarriage cases
Published in Journal of Obstetrics and Gynaecology, 2018
Luciana Bueno de Freitas, Christiane Curi Pereira, Paulo Roberto Merçon-de-Vargas, Liliana Cruz Spano
The infectious event could be responsible for dysfunctions in the basal intermediate trophoblast ability to invade the uterine wall, an essential step for establishing the high-flow, the low-resistance maternal–placental circulation needed to supply the placenta and foetus. A failed invasion by the extravillous trophoblast cells could lead to placental dysfunction and to adverse obstetric outcomes, including foetal growth restriction, pre-eclampsia, premature rupture of membranes at term and a spontaneous preterm delivery (Germain et al. 1999; Cho et al. 2013). Moreover, the embryo development could be affected by HPV when an infection occurs at the earlier stages (Henneberg et al. 2006). Therefore, an HPV infection of trophoblastic and decidual cells may induce an abnormal placentation disruption by the above mechanisms and may lead to the adverse gestational consequences. Indeed, although variable grades of inflammation were observed in two-thirds of the cases, only one had HPV positivity showing chronic villitis with lymphohystiocytic inflammatory exudate, suggesting a possible viral damaging action. Actually, considering the peculiar cell restriction for HPV replication, its association with miscarriage remains a concern, highlighting the importance of elucidating whether in fact a miscarriage can be caused by the most common virus that infects the genital tract.
Advances in current and emerging therapeutics for gestational trophoblast malignancies
Published in Expert Opinion on Orphan Drugs, 2019
PSTT and ETTs are rarer diagnoses with a combined incidence of less than 10 cases annually in the United Kingdom. These malignancies are thought to occur from malignant change within the implantation site intermediate trophoblast cells at around day 14 in development [16]. Generally, PSTT and ETT are slower growing malignancies compared to gestational choriocarcinoma and often present with either PV bleeding or amenorrhea secondary to their production of hCG [17]. Overall, PSTT and ETT make relatively low levels of hCG, have a lower sensitivity to chemotherapy and while a proportion of patients can be cured with surgery, or the combination of surgery and chemotherapy, the overall cure rates are significantly lower than in gestational choriocarcinoma [18].